Investigations will be performed mainly on xenografts of human tumors growing in immune-suppressed mice, on the Lewis lung tumor, and on certain normal tissues of the mouse. They will be designed to elucidate the response of tumors to combine treatment with radiotherapy and chemotherapy. A range of established and new cancer chemotherapeutic agents will be given before, during, or after a simple course of fractionated irradiation. In the tumors, evidence will be sought for drugs that induce reoxygenation and that can exploit tumor cell repopulation. These modes of action will be sought by a comparison of results when drugs are given befoe, concurrently with, and after irradiation. The normal tissue studies will be directly parallel, investigating the enhancement of radiation damage to skin, lung, intestine, and spinal cord as a result of the three modes of drug combination. End-points will include tumor growth-delay and gross end-points of normal tissue damage. In addition, assays for clonogenic cell survival will be used to explore interesting phenomena in more detail. These are available both for the Lewis lung tumor and for some xenografted tumors, and will mainly be used to investigate shoulder-reduction, changes in DO and hypoxic fraction, as well as modifications in drug sensitivity after irradiation.